Senescence Process Research Articles

Stress Hormones: Unveiling the Role in Accelerated Cellular Senescence.

Cellular senescence is a complex process involving multiple factors, such as genetics, environment, and behavior. However, recent studies have shown that stress also plays a crucial role in inducing cellular senescence. Stress can affect cellular function and structure through various pathways, leading to accelerated aging. Exposure to stressful conditions can alter the neuroendocrine system, activate the hypothalamus-pituitary-adrenal axis and sympathetic adrenal medullary axis, and release cortisol and catecholamines, causing mitochondrial dysfunction, generating excessive reactive oxygen species, and inducing oxidative stress, DNA damage, and inflammatory reactions, ultimately resulting in accelerated cellular senescence. The process of stress-induced cellular senescence has been implicated in a number of chronic diseases, including age-related macular degeneration, chronic kidney disease, type 2 diabetes, cardiovascular disease and obstructive sleep apnea. In this review, we integrate recent progress research progress in our understanding of the mechanisms of stress-induced cellular senescence and discuss its underlying mechanisms from the perspective of stress hormones. We review potential therapeutic targets for stress-induced premature senescence and discuss the advantages and limitations of existing pharmacological agents capable of ameliorating stress-induced premature senescence.

Image processing and supervised machine learning for retinal microglia characterization in senescence.

The process of senescence impairs the function of cells and can ultimately be a key factor in the development of disease. With an aging population, senescence-related diseases are increasing in prevalence. Therefore, understanding the mechanisms of cellular senescence within the central nervous system (CNS), including the retina, may yield new therapeutic pathways to slow or even prevent the development of neuro- and retinal degenerative diseases. One method of probing the changing functions of senescent retinal cells is to observe retinal microglial cells. Their morphological structure may change in response to their surrounding cellular environment. In this chapter, we show how microglial cells in the retina, which are implicated in aging and diseases of the CNS, can be identified, quantified, and classified into five distinct morphotypes using image processing and supervised machine learning algorithms. The process involves dissecting, staining, and mounting mouse retinas, before image capture via fluorescence microscopy. The resulting images can then be classified by morphotype using a support vector machine (SVM) we have recently described showing high accuracy. This SVM model uses shape metrics found to correspond with qualitative descriptions of the shape of each morphotype taken from existing literature. We encourage more objective and widespread use of methods of quantification such as this. We believe automatic delineation of the population of microglial cells in the retina, could potentially lead to their use as retinal imaging biomarkers for disease prediction in the future.

Impact and potential value of immunosenescence on solid gastrointestinal tumors.

Solid gastrointestinal tumors often respond poorly to immunotherapy for the complex tumor microenvironment (TME), which is exacerbated by immune system alterations. Immunosenescence is the process of increased diversification of immune genes due to aging and other factors, leading to a decrease in the recognition function of the immune system. This process involves immune organs, immune cells, and the senescence-associated secretory phenotype (SASP). The most fundamental change is DNA damage, resulting in TME remodeling. The main manifestations are worsening inflammation, increased immunosuppressive SASP production, decreased immune cell antitumor activity, and the accumulation of tumor-associated fibroblasts and myeloid-derived suppressor cells, making antitumor therapy less effective. Senotherapy strategies to remove senescent cells and block key senescence processes can have synergistic effects with other treatments. This review focuses on immunoenescence and its impact on the solid TME. We characterize the immunosenescent TME and discuss future directions for antitumor therapies targeting senescence.

Ecophysiological responses of bromelias in the restinga in simulated climate change scenarios.

We investigated the ecophysiological responses of the bromeliads Aechmea nudicaulis and Vriesea procera, seeking to assess their suitability to survive in a climate change scenario (optimistic scenario RCP 2.6 of the IPCC, 2021) in a Restinga environment. To carry out this investigation, we used open-top chambers (OTC). During a period of nine months (June 2022 to February 2023), the bromeliads A. nudicaulis and V. procera were subjected to the following treatments: treatment T: plants transplanted to the environmental conditions of the bare sand of the restinga and subjected to the microclimatic conditions of the OTC's; control C: plants transplanted to the environmental conditions of the bare sand of the restinga. The ecophysiological variables height, rosette diameter, relative water content, specific leaf area and total weight of the plants were evaluated. In addition, dead plants were counted. The OTC's showed an average increase in temperature and VPD (Vapor Pressure Deficit) of 1.6°C and 0.5 Kpa, respectively, and an average reduction in RH (relative humidity) of 5.3%. The results of this study indicated that the increase in local temperature that occurred between the sixth and seventh months evaluated (November and December) created limiting conditions that exceeded the tolerance capacity of the bromeliads studied. Furthermore, the climatic conditions of the OTCs intensified the damage that occurred in the plants, verified here by the reductions in the values ​​of the ecophysiological attributes evaluated in the bromeliads studied. In addition, the high mortality rate (above 50%) reinforces the idea that the climatic conditions of the OTC's induced the bromeliads studied to a senescence process. Therefore, these results are important, as they indicate that even the most optimistic climate change scenario (IPCC 2021 RCP 2.6) can harm the growth and development of these bromeliads, which are essential for the structure and functioning of Restinga communities.

Effect of modified atmosphere package on attributes of sweet bamboo shoots after harvest.

Tender bamboo shoots undergo rapid senescence that influences their quality and commercial value after harvest. In this study, the tender sweet bamboo shoots ('Wensun') were packed by a passive modified atmosphere packaging (PMAP) to inhibit the senescence process, taking polyethylene package as control. The increase in CO2 and the decrease in O2 gas concentrations in the headspace atmosphere of the packages were remarkably modified by PMAP treatments. The modified gas atmosphere packaging inhibited the changes in firmness, as well as the content of cellulose, total pectin, and lignin in the cell walls of bamboo shoots. The enzymatic activities of cellulase, pectinase, and polygalacturonase that act on cell wall polysaccharides, and phenylalanine ammonia lyase, cinnamyl alcohol dehydrogenase, peroxidase, and laccase regulating the lignin biosynthesis were modified by PMAP treatment different from control during storage. The expression levels of the lignin biosynthesis genes PePAL3/4, PeCAD, Pe4CL5, PeC4H, PeCCOAOMT, PeCOMT, cellulose synthase PeCESA1, and related transcription factors PeSND2, PeKNAT7, PeMYB20, PeMYB63, and PeMYB85 were clearly regulated. These results suggest that PMAP efficiently retards the changes in lignin and cell wall polysaccharides, thus delaying the senescence of tender sweet bamboo shoots during storage.

Effects of Alginate-based Chitosan-Starch Coating on the Physico-Chemical Properties of Guapple (Psidium guajava L. cv. Queso de Bola)

Because of its nutritious qualities and growing demands, an attempt to support the Philippine Guapple industry was enacted through edible coating. Especially those of starch and chitosan formulation, edible coatings are known to develop low-cost and biocompatible resistance from the drastic changes that commodities experience from their surroundings. Thus, becoming a low-cost technology to prevent yield losses and decrease rate of senescence for selected fruits. With the control treatment as the designated Treatment 1, Treatment 2 Guapples are treated with coating concentrations of 2% Alginate + 0.5% Chitosan, and Treatment 3 Guapples are those that have been treated with 2% Alginate + 0.5% Chitosan + 2% Starch. This setup identifies if the variations of Starch and Chitosan concentrations affect the overall postharvest qualities of Guapples. The physico-chemical parameters were measured through non-destructive and destructive tests, as they relate to the overall process of senescence. Replicated four times in ambient conditions (28°C, ~80% RH ), the physico-chemical variables are recorded periodically in a span of one week. It was found that in moisture loss deterrence, the coating from Treatment 2 is the most effective, with significant moisture loss deterrence (vs. Control) found during Day 2. On the other hand, it was found that in preserving the Guapples from Browning, Treatment 3 does it slightly better. No other significant changes were found in terms of other chemical properties of Guapple such as Total Soluble Solids, Titratable Acidity, pH, Firmness, and Ripening Index. Furthermore, the consumer sensory evaluation suggests that they are unable to find any significant preferential difference, except for slight preferences in Visual Quality found in Guapples with Treatment 3. Moving forward, maintaining temperature in the laboratory is recommended as it is determined to be a confounding variable that may have affected results in a warm June climate.

Antioxidant Systems and Quality in Sweet Cherries Are Improved by Preharvest GABA Treatments Leading to Delay Postharvest Senescence.

γ-Aminobutyric acid (GABA) plays important roles in plant development, including the maintenance of fruit quality when applied as postharvest treatment. However, little information is available about the effects of preharvest GABA treatments. Thus, GABA (10, 50 and 100 mM) was applied as foliar spray at key points of fruit development in three sweet cherry cultivars and over two years. The results show that quality parameters, such as total soluble solid content, titratable acidity and firmness were higher in the fruit from GABA-treated trees than in the controls, either at harvest or during four weeks of cold storage. In addition, the total phenolic and total and individual anthocyanin concentrations were also enhanced by GABA treatments and the fruit color was improved. The activities of the antioxidant enzymes catalase, ascorbate peroxidase and peroxidase were also enhanced by the GABA treatments. The most effective concentration was 50 mM, which led to extending the storage period of sweet cherries with high quality traits to up to four weeks, while for the controls this was two weeks. Thus, GABA treatment had a clear effect on delaying the postharvest ripening and senescence processes in sweet cherries, with an additional effect on enhancing the content of bioactive compounds, such as phenolics and anthocyanins, with antioxidant properties and health benefits.

Potato Leaf Chlorophyll Content Estimation through Radiative Transfer Modeling and Active Learning

Leaf chlorophyll content (LCC) significantly correlates with crop growth conditions, nitrogen content, yield, etc. It is a crucial indicator for elucidating the senescence process of plants and can reflect their growth and nutrition status. This study was carried out based on a potato nitrogen and potassium fertilizer gradient experiment in the year 2022 at Keshan Farm, Qiqihar Branch of Heilongjiang Agricultural Reclamation Bureau. Leaf hyperspectral and leaf chlorophyll content data were collected at the potato tuber formation, tuber growth, and starch accumulation periods. The PROSPECT-4 radiative transfer model was employed to construct a look-up table (LUT) as a simulated data set. This was accomplished by simulating potato leaves’ spectral reflectance and chlorophyll content. Then, the active learning (AL) technique was used to select the most enlightening training samples from the LUT based on the measured potato data. The Gaussian process regression (GPR) algorithm was finally employed to construct the inversion models for the chlorophyll content of potato leaves for both the whole and single growth periods based on the training samples selected by the AL method and the ground measured data of the potatoes. The R2 values of model validation accuracy for the potato whole plantation period and three single growth periods are 0.742, 0.683, 0.828, and 0.533, respectively with RMSE values of 4.207, 4.364, 2.301, and 3.791 µg/cm2. Compared with the LCC inversion accuracy through LUT with a cost function, the validation accuracies of the GPR_PROSPECT-AL hybrid model were improved by 0.119, 0.200, 0.328, and 0.255, and the RMSE were reduced by 3.763, 2.759, 0.118, and 5.058 µg/cm2, respectively. The study results indicate that the hybrid method combined with the radiative transfer model and active learning can effectively select informative training samples from a data pool and improve the accuracy of potato LCC estimation, which provides a valid tool for accurately monitoring crop growth and growth health.

Cellular microenvironment: a key for tuning mesenchymal stem cell senescence.

Mesenchymal stem cells (MSCs) possess the ability to self-renew and differentiate into multiple cell types, making them highly suitable for use as seed cells in tissue engineering. These can be derived from various sources and have been found to play crucial roles in several physiological processes, such as tissue repair, immune regulation, and intercellular communication. However, the limited capacity for cell proliferation and the secretion of senescence-associated secreted phenotypes (SASPs) pose challenges for the clinical application of MSCs. In this review, we provide a comprehensive summary of the senescence characteristics of MSCs and examine the different features of cellular microenvironments studied thus far. Additionally, we discuss the mechanisms by which cellular microenvironments regulate the senescence process of MSCs, offering insights into preserving their functionality and enhancing their effectiveness.

Diffusion-sensitized magnetic resonance imaging highlights placental microstructural damage in patients with previous SARS-CoV-2 pregnancy infection

IntroductionSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been a major global health problem since December 2019. This work aimed to investigate whether pregnant women's mild and moderate SARS-CoV-2 infection was associated with microstructural and vascular changes in the placenta observable in vivo by Intravoxel Incoherent Motion (IVIM) at different gestational ages (GA). MethodsThis was a retrospective, nested case-control of pregnant women during the SARS-CoV-2 pandemic (COVID-19 group, n = 14) compared to pre-pandemic healthy controls (n = 19). MRI IVIM protocol at 1.5T was constituted of diffusion-weighted (DW) images with TR/TE = 3100/76 ms and 10 b-values (0,10,30,50,75,100,200,400,700,1000s/mm2). Differences between IVIM parameters D (diffusion), and f (fractional perfusion) quantified in the two groups were evaluated using the ANOVA test with Bonferroni correction and linear correlation between IVIM metrics and GA, COVID-19 duration, the delay time between a positive SARS-CoV-2 test and MRI examination (delay-time exam+) was studied by Pearson-test. ResultsD was significantly higher in the COVID-19 placentas compared to that of the age-matched healthy group (p < 0.04 in fetal and p < 0.007 in maternal site). No significant difference between f values was found in the two groups suggesting no-specific microstructural damage with no perfusion alteration (potentially quantified by f) in mild/moderate SARS-Cov-2 placentas. A significant negative correlation was found between D and GA in the COVID-19 placentas whereas no significant correlation was found in the control placentas reflecting a possible accelerated senescence process due to COVID-19. DiscussionWe report impaired microstructural placental development during pregnancy and the absence of perfusion-IVIM parameter changes that may indicate no perfusion changing through microvessels and microvilli in the placentas of pregnancies with mild/moderate SARS-Cov-2 after reaching negativity.

Application of 1-MCP does not slow down the ripening process of Mango (Mangifera indica L)

Fruits and vegetables are perishable so that they are easily degraded and thus have a short shelf life. Some studies have been carried out intensively to extend the shelf life of fruit with the application of 1-methylcyclopropene (1-MCP) which is an ethylene inhibitor (indirectly) to slow down the ripening process and extend its shelf life. The benefits of using 1-MCP to delay fruit softening have also been published, however the inhibition of ripening and fruit softening by 1-MCP in mango (Mangifera indica) is very limited. 1-MCP delays fruit softening during storage by indirectly inhibiting ethylene synthesis and slowing the activity of cell wall-damaging enzymes, such as pectin methyl esterase (PME). To study the effect of 1-MCP on mango fruit quality and its shelf life, the experiment was carried out by measuring weight loss, colour, firmness, vitamin C, total soluble solids, titratable acidity, and reducing sugars periodically. For all fruit samples, the pulp was chopped, frozen in liquid nitrogen, and then stored at 8°C until further use. The results showed that application of 1-MCP at room temperature did not slow down neither the senescence process nor the shelf life of mango fruit on weight loss, colour, firmness, vitamin C, total soluble solids, titratable acidity, and reducing sugars parameters.

Iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway

Cellular senescence is a hallmark of aging and has been linked to age-related diseases. Age-related macular degeneration (AMD), the most common aging-related retinal disease, is prospectively associated with retinal pigment epithelial (RPE) senescence. However, the mechanism of RPE cell senescence remains unknown. In this study, tert-butyl hydroperoxide (TBH)-induced ARPE-19 cells and D-galactose-treated C57 mice were used to examine the cause of elevated iron in RPE cell senescence. Ferric ammonium citrate (FAC)-treated ARPE-19 cells and C57 mice were used to elucidated the mechanism of iron overload-induced RPE cell senescence. Molecular biology techniques for the assessment of iron metabolism, cellular senescence, autophagy, and mitochondrial function in vivo and in vitro. We found that iron level was increased during the senescence process. Ferritin, a major iron storage protein, is negatively correlated with intracellular iron levels and cell senescence. NCOA4, a cargo receptor for ferritinophagy, mediates degradation of ferritin and contributes to iron accumulation. Besides, we found that iron overload leads to mitochondrial dysfunction. As a result, mitochondrial DNA (mtDNA) is released from damaged mitochondria to cytoplasm. Cytoplasm mtDNA activates the cGAS-STING pathway and promotes inflammatory senescence-associated secretory phenotype (SASP) and cell senescence. Meanwhile, iron chelator Deferoxamine (DFO) significantly rescues RPE senescence and retinopathy induced by FAC or D-gal in mice. Taken together, these findings imply that iron derived from NCOA4-mediated ferritinophagy causes cellular senescence via the cGAS-STING pathway. Inhibiting iron accumulation may represent a promising therapeutic approach for age-related diseases such as AMD.

Imaging the skin epilipidome and the activity of metabolic key enzymes in the senescence process at single cell level

Imaging the skin epilipidome and the activity of metabolic key enzymes in the senescence process at single cell level

DNA damage response(DDR): a link between cellular senescence and human cytomegalovirus.

The DNA damage response (DDR) is a signaling cascade that is triggered by DNA damage, involving the halting of cell cycle progression and repair. It is a key event leading to senescence, which is characterized by irreversible cell cycle arrest and the senescence-associated secretory phenotype (SASP) that includes the expression of inflammatory cytokines. Human cytomegalovirus (HCMV) is a ubiquitous pathogen that plays an important role in the senescence process. It has been established that DDR is necessary for HCMV to replicate effectively. This paper reviews the relationship between DDR, cellular senescence, and HCMV, providing new sights for virus-induced senescence (VIS).

Does the interplay between human endogenous retrovirus K and extracellular vesicles contribute to aging?

The role of extracellular vesicles (EVs), including retroviral-like particles (RVLPs), in pathogenic processes is currently a subject of active investigation. Several studies have identified mechanistic links between the increased presence of EVs and the process of senescence. A recent study reveals that the reverse transcribed complementary DNA (cDNA) of a human endogenous retroviral sequence can activate the innate immune system and result in tissue damage and/or the spread of cellular senescence to distant tissues. Several studies have linked EVs to age-related diseases, such as Alzheimer's disease and Parkinson's disease, and have included isolation of EVs from individuals with these diseases. Loss of epigenetic regulation, immune activation, and environmental stimuli can all lead to the expression of endogenous retroviruses and the incorporation of their proteins and transcripts into EVs. In addition, EVs disseminating these endogenous retroviral components have now been shown to act in a paracrine manner in multiple human diseases. Further investigation of the connection between EVs containing endogenous retroviral protein products or nucleotides should be pursued in models of age-related diseases.

Anti-aging Factor GRSF1 Attenuates Cerebral Ischemia-Reperfusion Injury in Mice by Inhibiting GPX4-Mediated Ferroptosis.

Abnormal accumulation of senescent cells in tissues has been shown to facilitate the onset and progression of various diseases. As an important protein involving in the regulation of cellular senescence process, researches suggested GRSF1 as a potential senolytic target to improve multiple physiological and pathological processes. However, the underlying mechanism of cellular senescence on cerebral ischemia-reperfusion injury (CIRI) has not been revealed. Here, we investigated the effect of GRSF1 on CIRI and delved into its specific mechanisms. In the present study, we established a mouse model of cerebral ischemia-reperfusion (CIR) and observed low expression of anti-aging factor GRSF1, along with greatly increased levels of senescence-related markers p16 and p21 and senescence-associated secretory phenotype TNF-α. Furthermore, we found that the expression of GPX4 was elevated parallel to GRSF1 in CIR mice with overexpression of GRSF1, oxidative stress, and iron metabolism-related proteins were inhibited. Functionally, overexpressing GRSF1 significantly ameliorated infarct volume and neurological function scores and suppressed apoptosis in CIR mice, while administration of GPX4 inhibitors reversed these beneficial phenotypes. Taken together, our results indicate cellular senescence as an important pathological mechanism to exacerbate cerebral injury during CIRI, while GRSF1 could inhibit oxidative stress-mediated ferroptosis through upregulating GPX4 to attenuate reperfusion injury, which makes senolytic treatment, especially GRSF1, a promising therapeutic target for CIRI.

Lactoferrin improves symptoms of dextran sulfate sodium-induced colitis in mice through modulation of cellular senescence

The multifaceted effects of lactoferrin (LF) on the digestive and immune systems make it an attractive therapeutic option in inflammatory bowel diseases. In this study, we aimed to explore the anti-inflammatory effects of LF in colitis, particularly in relation to cellular senescence. We hypothesize that LF has the potential to modulate the senescence process. The effects of LF on senescence were tested in vitro using HCT116 and SW480 cell lines, and in vivo, the dextran sulfate sodium–induced mouse model of colitis. LF (500 mg/kg) alleviated symptoms of colitis in mice with a significant decrease in colon damage (P < .0001 vs. control) and microscopic (P < .05 vs. control) scores. Cellular senescence markers p16 and p21 were significantly upregulated in the mouse colon during inflammation (both P < .01 vs. control), and LF at 500 mg/kg decreased these markers (both P < .05 vs. dextran sulfate sodium–treated mice). In vitro, LF significantly affected the expression of p16 and p21 (P < .05–P < .0001 vs. control), senescence associated secretory phenotype (P < .01–P < .0001 vs. control), and telomere-specific proteins: telomeric repeat binding factor 1 and 2 (P < .05–P < .0001 vs. control) in a concentration-dependent manner. LF modulates the expression of cellular senescence markers and shows hallmarks of senolytic and pro-senescent activity, depending on dose. Further studies are needed to fully understand the anti-inflammatory effect of LF in the context of senescence and safe utilization in patients with inflammatory bowel diseases.

New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death.

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals and metabolites in the circulatory system. The senescence and death of ECs are not only adverse outcomes, but also causal contributors to endothelial dysfunction, an early risk marker of atherosclerosis. The pathophysiological process of EC senescence involves both structural and functional changes and has been linked to various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, and aberrant metabolite sensing and signaling. Multiple forms of EC death have been documented in atherosclerosis, including autophagic cell death, apoptosis, pyroptosis, NETosis, necroptosis, and ferroptosis. Despite this, the molecular mechanisms underlying EC senescence or death in atherogenesis are not fully understood. To provide a comprehensive update on the subject, this review examines the historic and latest findings on the molecular mechanisms and functional alterations associated with EC senescence and death in different stages of atherosclerosis.

In Situ Visible Spectroscopic Daily Monitoring of Senescence of Japanese Maple (Acer palmatum) Leaves.

The degradation of green leaves in autumn after their photosynthetic activities is associated with decreases in chlorophylls and increases in anthocyanins. However, the sequential orders of these processes are not well understood because of a lack of continuous monitoring of leaves in the same positions. Therefore, the senescence processes of Japanese maple (Acer palmatum) leaves were followed daily in the same positions for approximately 60 days using visible spectroscopy with an original handheld visible-near-infrared spectrometer. The obtained reflection spectra were converted to absorption spectra and band areas of chlorophyll a and anthocyanins were determined. Decreases in the chlorophyll a band area with time show two-step exponential decreases corresponding to slow and fast first-order decrease rates. A rapid decrease in chlorophyll a started after an increase in anthocyanin. Therefore, the leaf senescence started through a slow decrease in chlorophyll a (20-30 days), followed by a rapid increase in anthocyanins (~20 days), followed by a rapid decrease in chlorophyll a (10-20 days). The formation of anthocyanins has been proposed to protect leaf cells from losing chlorophylls through solar radiation damage. The obtained sequential changes of pigments support this light screen hypothesis. (199 words < 200 words).

Selected phenolic compounds in the modulation of biochemical pathways involved in aging

Graphical abstract Abstract The use of phenolic compounds, derived by plants, has recently emerged as a promising approach to prolong the lifespan by modulating metabolic pathways involved in aging. Phenolic compounds possess a broad spectrum of biochemical and pharmacological effects beneficial to human health such as modulating cellular senescence processes by interacting with molecular targets that regulate aging-related pathways. Phenolic compounds represent the major phytochemicals in our diet and possess several biological activities such as antioxidant and anti-inflammatory effects; protection against aging-related diseases (cancer, diabetes and cardiovascular diseases) with potential therapeutic applications and this could suggest that these compounds could be used as anti-aging nutraceutical support. In this review, we have considered the possible effects of some phenolic compounds in different aging pathways, to provide an overview of recent knowledge on their anti-aging mechanism of action.